The aim of our research is an understanding of the function of several large assemblies of macromolecules of major biological importance. This understanding requires the determination of the structure of these specimens to high resolution. We have begun, collaboratively, to establish in the School of Medicine of the University of Pennsylvania a facility for structural study of biological specimens by high resolution electron microscopy and Fourier processing of electron microscope images. This proposal is for a densitometer that will allow us to digitize electron micrographs obtained by newer structure-preserving methods. These methods rely on low electron dose, maintaining native hydrated conformations in unstained specimens, and minimizing radiation damage by microscopy at liquid nitrogen temperatures. The major group of users all have substantial experience in protein structure analysis, biophysics, high resolution electron microscopy and image processing of electron micrographs. The structures which will be analyzed include: a) microtubules and their associated proteins; b) resting and altered mechanical states of eukaryotic flagella; c) vertebrate skeletal muscle myosin filaments; d) crystals of blood clotting proteins including fibrinogen/fibrin, Factors V, VIII, and XIII; e) intrinsic membrane proteins involved in bioenergetics, including cytochrome and oxidase from mitochondria, and photosynthetic reaction centers from R. sphaeroides.